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Characterisation of Strain Variation in Campylobacter jejuni - OZ0604(1)

Description
Campylobacter species, particularly Campylobacter jejuni, are a major cause of human gastro-enteritis in the UK and elsewhere. In the majority of infections, which are sporadic, the precise epidemiology is not determined, although several food producing animals have been implicated as important sources of infection. The epidemiology of zoonotic transmission of C. jejuni to man remains obscure due to inconsistencies within and between the various phenotyping and molecular typing methods used to characterise C. jejuni isolates. These inconsistencies arise from the inability of the current methods to unambiguously define strain types and genetic lineages, and the lack of precise understanding of the variation which they index. This work will address these problems, definitively establishing the range and mechanisms of genetic variability in populations of C. jejuni, by the application of the most recently developed sequence typing technologies to a minimum of 1500 isolates, representative of those obtained from human infections, farm animals, the human food chain, and the environment. Multilocus sequence typing (MLST), which identifies strain relationships on the basis of neutral variation in housekeeping genes, and antigen gene sequence typing, which will be used to elucidate the antigenic repertoire of this bacterium at one antigen locus, will provide an accurate, comprehensive, and portable typing system for C. jejuni and related organisms, with a firm theoretical basis in bacterial population biology. These data will permit the resolution of inconsistencies among the current methods used for C. jejuni strain characterisation. The data and methodologies will be made available to other laboratories by means of the world wide web (http://mlst.zoo.ox.ac.uk). Because of the unambiguous and auditable nature of nucleotide sequence data this will enable global epidemiology for these organisms without the difficulties of strain exchange and data comparison experienced by other typing systems. A further advantage of the sequence typing approach is that the data obtained can be used directly in studies of population genetics and evolution, which are essential for the development and implementation of informed public health intervention. The practical and theoretical approaches to be used in this work have been developed, validated, and refined at WTCEID in Oxford for other pathogens and, with the availability of genome sequence data from C. jejuni, provide an opportunity to obtain a detailed understanding of the genetic variability of C. jejuni and related species. Simultaneously, this study will produce a comprehensive typing scheme, which will be transferred to, and validated in, veterinary laboratories. These two advances will enable more precise disease surveillance and the development of public health policy on the basis of sound practical and theoretical appreciation of the biology of this organism. Further, the data will be analysed with the latest phylogenetic techniques to establish the mechnaisms of genetic variation in this organism. Finally, the methods to be used have the potential to be developed for use in routine diagnosis, epidemiology, and quality control.
Objective
1. To develop, by means of MLST and antigen sequence typing, a comprehensive description of genetic and antigenic variability in C. jejuni.
2. To Produce a database cataloguing the variability of this organism, accessible from the world wide web, to be disseminate the methodology developed and data obtained in 1.
3. To establish models of C. jejuni population biology.
4. To analyse the data with appropriate phylogenetic and theoretical techniques to determine the factors involved in genetic variation of C. jejuni.









Time-Scale and Cost
From: 1999

To: 2005

Cost: £774,549
Contractor / Funded Organisations
University - Oxford
Keywords
Animal Health              
Biotechnology              
Campylobacter              
Epidemiology              
Plants and Animals              
Zoonoses              
Fields of Study
Animal Health